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2018 年度 実績報告書

First neuronal guidance lipid: Elucidation of biosynthesis and development of lead compounds to support neuronal recovery after injury

研究課題

研究課題/領域番号 16K08259
研究機関国立研究開発法人理化学研究所

研究代表者

GREIMEL PETER  国立研究開発法人理化学研究所, 脳神経科学研究センター, 専任研究員 (60525541)

研究期間 (年度) 2016-04-01 – 2019-03-31
キーワードPhosphatidylglucoside / GPCR / Lipids / GPR55
研究実績の概要

G protein-coupled receptor 55 (GPR55) is highly expressed in brain and peripheral nervous system. It was originally deorphanized as a cannabinoid receptor, but has recently been described as a lysophospholipid-responsive receptor, responsive to lysophosphatidylinositol and lysophosphatidyl-β-D-glucoside (LysoPtdGlc). To characterize lysolipid-GPR55 interaction a novel homology model of GPR55 was created, based on the human δ-opioid, human adenosine A2A, and CXCR4 receptor. Additionally synthetic access to LysoPtdGlc and selected analogues featuring not only modifications on the acyl chain, but also on the phosphate moiety were established. The biological activity of each synthetic lipid was assessed using a GPR55-dependent chemotropism assay in primary sensory neurons. Molecular dynamics simulations of the GPR55 homology model embedded in a suitable lipid membrane and in presence of a variety of synthetic lysolipid ligands have been performed and assessed. Combination of the molecular dynamics simulations and biological experiments provided insight into the potential ligand entry port and binding pocket specifics of GPR55. These results highlight the preference for gluco- over inositol- and galacto-configured headgroups. Furthermore, the specific acyl chain length required for GPR55 activation has been determined and is in good agreement with the created homology model of GPR55.

  • 研究成果

    (6件)

すべて 2019 2018

すべて 雑誌論文 (5件) (うち国際共著 5件、 査読あり 5件、 オープンアクセス 2件) 学会発表 (1件) (うち国際学会 1件)

  • [雑誌論文] Formation of tubules and helical ribbons by ceramide phosphoethanolamine-containing membranes2019

    • 著者名/発表者名
      Inaba Takehiko、Murate Motohide、Tomishige Nario、Lee Yan-Fen、Hullin-Matsuda Fran?oise、Pollet Brigitte、Humbert Nicolas、M?ly Yves、Sako Yasushi、Greimel Peter、Kobayashi Toshihide
    • 雑誌名

      Scientific Reports

      巻: 9 ページ: 5812

    • DOI

      10.1038/s41598-019-42247-1

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Biophysical Properties of Phosphtidylglucoside and Phosphatidylinositol: Specific Differences in Head Group Interaction2018

    • 著者名/発表者名
      Greimel Peter
    • 雑誌名

      Trends in Glycoscience and Glycotechnology

      巻: 30 ページ: E1~E13

    • DOI

      https://doi.org/10.4052/tigg.1704.1E

    • 査読あり / 国際共著
  • [雑誌論文] Squaryl group modified phosphoglycolipid analogs as potential modulators of GPR552018

    • 著者名/発表者名
      Ding Feiqing、Guy Adam T.、Greimel Peter、Hirabayashi Yoshio、Kamiguchi Hiroyuki、Ito Yukishige
    • 雑誌名

      Chemical Communications

      巻: 54 ページ: 8470~8473

    • DOI

      10.1039/c8cc04467h

    • 査読あり / 国際共著
  • [雑誌論文] GPRC5B-Mediated Sphingomyelin Synthase 2 Phosphorylation Plays a Critical Role in Insulin Resistance2018

    • 著者名/発表者名
      Kim Yeon-Jeong、Greimel Peter、Hirabayashi Yoshio
    • 雑誌名

      iScience

      巻: 8 ページ: 250~266

    • DOI

      10.1016/j.isci.2018.10.001

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Preference for Glucose over Inositol Headgroup during Lysolipid Activation of G Protein-Coupled Receptor 552018

    • 著者名/発表者名
      Guy Adam T.、Kano Koki、Ohyama Jyunpei、Kamiguchi Hiroyuki、Hirabayashi Yoshio、Ito Yukishige、Matsuo Ichiro、Greimel Peter
    • 雑誌名

      ACS Chemical Neuroscience

      巻: 10 ページ: 716~727

    • DOI

      10.1021/acschemneuro.8b00505

    • 査読あり / 国際共著
  • [学会発表] Phosphatidyl-β-D-glucoside: From Biosynthesis to Biological Activity of Synthetic Analogues2018

    • 著者名/発表者名
      P. Greimel, A.T. Guy, H.H. Hung, Y. Nagatsuka, I. Matsuo, Y. Ito, H. Kamiguchi, Y. Hirabayashi
    • 学会等名
      29th International Carbohydrate Conference
    • 国際学会

URL: 

公開日: 2019-12-27  

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